Clinical data from studies involving novel antibiotics to treat multidrug-resistant Gram-negative bacterial infections

Autores organización

• 

  Maria Virginia Villegas Botero

  Autor

Autores

• Kanj SS
• Bassetti M
• Kiratisin P
• Rodrigues C
• Yu Y
• van Duin D

Grupos de investigación

• Grupo de Investigación en Resistencia Antimicrobiana y Epidemiología Hospitalaria RAEH

  

  Investigador

  Maria Virginia Villegas Botero

Resumen

Multidrug-resistant (MDR) Gram-negative bacteria (GNB) pose a critical threat to global healthcare, worsening outcomes and increasing mortality among infected patients. Carbapenemase- and extended-spectrum ß-lactamase-producing Enterobacterales, as well as carbapenemase-producing Pseudomonas and Acinetobacter spp., are common MDR pathogens. New antibiotics and combinations have been developed to address this threat. Clinical trial findings support several combinations, notably ceftazidime–avibactam (CZA, a cephalosporin-ß-lactamase inhibitor combination), which is effective in treating complicated urinary tract infections (cUTI), complicated intra-abdominal infections and hospital-acquired and ventilator-associated pneumonia caused by GNBs. Other clinically effective combinations include meropenem–vaborbactam (MVB), ceftolozane–tazobactam (C/T) and imipenem–relebactam (I–R). Cefiderocol is a recent siderophore ß-lactam antibiotic that is useful against cUTIs caused by carbapenem-resistant Enterobacterales (CRE) and is stable against many ß-lactamases. Carbapenem-resistant Enterobacterales are a genetically heterogeneous group that vary in different world regions and are a substantial cause of infections, among which Klebsiella pneumoniae are the most common. Susceptible CRE infections can be treated with fluoroquinolones, aminoglycosides or fosfomycin, but alternatives include CZA, MVB, I–R, cefiderocol, tigecycline and eravacycline. Multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa are increasingly common pathogens producing a range of different carbapenemases, and infections are challenging to treat, often requiring novel antibiotics or combinations. Currently, no single agent can treat all MDR-GNB infections, but new ß-lactam–ß-lactamase inhibitor combinations are often effective for different infection sites and, when used appropriately, have the potential to improve outcomes. This article reviews clinical studies investigating novel ß-lactam approaches for treatment of MDR-GNB infections. © 2022

Copyright © 2022. Published by Elsevier Ltd.

Keywords

• Anti-Bacterial Agents; beta-Lactamase Inhibitors; Carbapenems; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacterial Infections; Humans; Microbial Sensitivity Tests; aminoglycoside; avibactam; avibactam plus ceftazidime; beta lactamase; beta lactamase inhibitor; carbapenem; carbapenemase; cefiderocol; ceftazidime; ceftolozane plus tazobactam; cephalosporinase; cilastatin sodium plus imipenem plus relebactam; colistin; fosfomycin; imipenem; levofloxacin; meropenem; meropenem plus vaborbactam; metronidazole; quinoline derived antiinfective agent; quinolone derivative; siderophore; tigecycline; antiinfective agent; beta lactamase inhibitor; carbapenem derivative; Acinetobacter; Acinetobacter baumannii; all cause mortality; Campylobacter; carbapenem resistant Acinetobacter baumannii; carbapenem resistant Pseudomonas aeruginosa; carbapenemase producing Enterobacteriaceae; drug efficacy; Escherichia coli; genetic susceptibility; Gram negative infection; human; intention to treat anal